Field
The present invention relates to a method for preventing the crystal precipitation of rotigotine in a composition for transdermal absorption containing rotigotine as an active ingredient, and more specifically, to a method for preparing a composition for transdermal absorption, the method comprising mixing rotigotine and an antioxidant at a weight ratio of 1:(0.0001-0.1); to a transdermal absorption preparation prepared by the method; and to a transdermal therapeutic system comprising a drug-containing adhesive layer containing rotigotine and an antioxidant at a weight ratio of 1:(0.0001-0.1), and a substrate for supporting the drug-containing adhesive layer.
Discussion of the Background
Rotigotine, (−)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphtahlenol, is used as a non-ergoline dopamine agonist for the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS).
Rotigotine has been commercially available as a transdermal patch. A transdermal patch having a rotigotine composition is disclosed in U.S. Pat. No. 7,413,747B. Also, a commercially available rotigotine patch employs a silicone adhesive, which is disclosed in EP 1033978B. However, the commercially available patch causes the precipitation of crystals of rotigotine under room-temperature storage conditions, and thus it is difficult to secure the storage period necessary for commercial distribution of such a patch. In order to solve the problem, WO 2011/076879 discloses a rotigotine transdermal composition with a polymer (such as polyvinylpyrrolidone) added thereto, but the use of such an additive may degrade the stability of rotigotine. In addition, the addition of a crystal precipitation inhibitor for preventing the crystal precipitation of rotigotine may degrade the transmittance of rotigotine. Thus, EP 1769785 discloses the use of a transmittance promoter, but the use of the transmittance promoter may also cause the destabilization of rotigotine. In order to solve the above problems, measures for stabilizing active materials have been continuously studied.